Approximately 1 million Americans are diagnosed with neoplasia every year, and about half a million people in the United States die of the disease annually. While improvements in neoplasia detection, diagnosis, and treatment have increased the survival rate for many types of neoplasia, only about 60 percent of people diagnosed with neoplasia are alive five years after treatment, making neoplasia the second leading cause of death in the United States. Cancer vaccines are one promising approach to treating neoplasia through induction of an immune response against tumor-associated antigens (TAA). However, immunological tolerance against self-antigens may limit an effective antitumor immune response.
CD4+CD25+ regulatory T cells (Treg) function in maintaining a balance between immune tolerance and immune responsiveness. Treg suppress pathologic and physiological immune response, contributing to the maintenance of immunological self-tolerance and immune homeostasis. In conditions, such as chronic infection and neoplasia, Treg suppressive activity undesirably reduces the efficacy of an immune response capable of fighting the infection or eliminating the neoplasia. Conversely, in conditions where an immune response is undesirably activity, such as autoimmunity and inflammatory disease, Treg suppressive activity is inadequate to reduce the undesirable immune response. Conventional methods for modulating an immune response are inadequate for the treatment of such conditions. Methods for modulating Tregs suppressive activity are urgently required, not only for the treatment of neoplasia, but also for the treatment of chronic infection and inflammation.